IL273432B - Protein degraders and uses thereof - Google Patents

Protein degraders and uses thereof

Info

Publication number
IL273432B
IL273432B IL273432A IL27343220A IL273432B IL 273432 B IL273432 B IL 273432B IL 273432 A IL273432 A IL 273432A IL 27343220 A IL27343220 A IL 27343220A IL 273432 B IL273432 B IL 273432B
Authority
IL
Israel
Prior art keywords
compound
nitrogen
cancer
membered
sulfur
Prior art date
Application number
IL273432A
Other languages
Hebrew (he)
Other versions
IL273432A (en
Original Assignee
Kymera Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kymera Therapeutics Inc filed Critical Kymera Therapeutics Inc
Publication of IL273432A publication Critical patent/IL273432A/en
Publication of IL273432B publication Critical patent/IL273432B/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/14—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Nutrition Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Claims (16)

1./ 5 CLAIMS We claim: 1. A compound of formula I : Ior a pharmaceutically acceptable salt thereof, wherein: X is a bivalent moiety selected from a covalent bond, –CH 2 –, –C(O) –, –C(S) –, or ; R is hydrogen, halogen, –CN, –OR, –SR, –S(O)R, –S(O) 2R, –NR 2, or an optionally substituted C 1-4 aliphatic; each R is independently hydrogen, R, halogen, –CN, –NO 2, –OR, -SR, -NR 2, -S(O) 2R, -S(O) 2NR 2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR 2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR 2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR 2, or –N(R)S(O) 2R; Ring A is a bicyclic ring selected from , , or ; Ring B is a fused ring selected from 6-membered aryl containing 0-2 nitrogen atoms, 5 to 7-membered partially saturated carbocyclyl, 5 to 7-membered partially saturated heterocyclyl with 1-heteroatoms independently selected from nitrogen, oxygen or sulfur, or 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur; R is independently hydrogen, R, halogen, –CN, –NO 2, –OR, -SR, -NR 2, -S(O) 2R, -S(O) 2NR 2, -S(O)R, -C(O)R, -C(O)OR, –C(O)NR 2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR 2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR 2, or –N(R)S(O) 2R; 273432/ 5 each R is independently an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 4-membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C 1-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by –Cy-, -O-, -NR-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O) 2-, -NRS(O) 2-, -S(O) 2NR-, -NRC(O)-, -C(O)NR-, -OC(O)NR-, – NRC(O)O-, , , , , or , wherein: each –Cy – is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroarylenyl having 1-heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBM is a target binding moiety, wherein the target binding moiety is a BRD4 binding moiety; m is 0, 1, 2, 3 or 4; each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and each R is independently hydrogen, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: 273432/ 5 two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.
2. The compound of claim 1, wherein X is –C(O) –.
3. The compound of claim 1, wherein R is hydrogen, halogen, –OR, –SR, –S(O)R, –S(O) 2R, –NR 2, or an optionally substituted C 1-4 aliphatic.
4. The compound of claim 1, wherein Ring A is .
5. The compound of claim 1, wherein Ring B is selected from 6-membered aryl containing 0-nitrogen atoms, 6-membered partially saturated carbocyclyl, or 6-membered partially saturated heterocyclyl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur.
6. The compound of claim 1, wherein R is hydrogen, R, halogen, –CN, –NO 2, –OR, -SR, -NR 2, -S(O) 2R, -S(O) 2NR 2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR 2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR 2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR 2, or –N(R)S(O) 2R.
7. The compound of claim 1, wherein L is a bivalent, saturated or unsaturated, straight or branched C 1-20 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by –Cy-, -O-, -NR-, -S-, -OC(O)-, -C(O)O-, -C(O)-, -S(O)-, -S(O) 2-, -NRS(O) 2-, -S(O) 2NR-, -NRC(O)-, -C(O)NR-, - OC(O)NR-, –NRC(O)O-, , , , , or . 273432/ 5
8. The compound of claim 1, wherein the BRD4 binding moiety is: or , wherein R denotes attachment to .
9. The compound of claim 1, wherein said compound is selected from I-9 , 273432/ 5 I-10 , I-35 , I-36 , I-37 , I-38 , or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition comprising a compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. 273432/ 5
11. A method of degrading a target protein in a biological sample comprising contacting the sample with the compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof.
12. The compound of any one of claims 1-9 or a pharmaceutical composition thereof for use in a method of treating a target protein-mediated disorder, disease, or condition in a patient comprising administering said compound or composition to said patient.
13. The compound or composition for use of claim 12, wherein the disorder is selected from an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.
14. The compound or composition for use of claim 13, wherein the disorder is a proliferative disorder.
15. The compound or composition for use of claim 14, wherein the proliferative disorder is a cancer.
16. The compound or composition for use of claim 15, wherein the cancer is squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, and renal cell carcinomas, cancer of the bladder, bowel, breast, cervix, colon, esophagus, head, kidney, liver, lung, neck, ovary, pancreas, prostate, and stomach; leukemias; benign and malignant lymphomas, particularly Burkitt's lymphoma and Non-Hodgkin's lymphoma; benign and malignant melanomas; myeloproliferative diseases; multiple myeloma, sarcomas, including Ewing's sarcoma, hemangiosarcoma, Kaposi's sarcoma, liposarcoma, myosarcomas, peripheral neuroepithelioma, synovial sarcoma, gliomas, astrocytomas, oligodendrogliomas, ependymomas, gliobastomas, neuroblastomas, ganglioneuromas, gangliogliomas, medulloblastomas, pineal cell tumors, meningiomas, meningeal sarcomas, neurofibromas, and Schwannomas; bowel cancer, breast cancer, prostate cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, testicular cancer, thyroid cancer, astrocytoma, esophageal cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, melanoma; carcinosarcoma, Hodgkin's disease, Wilms' tumor or teratocarcinomas, T-lineage Acute lymphoblastic Leukemia (T-ALL), T-lineage lymphoblastic Lymphoma (T-LL), Peripheral T-cell lymphoma, Adult T-cell Leukemia, Pre-B ALL, Pre-B Lymphomas, Large B-cell Lymphoma, 273432/ 5 Burkitts Lymphoma, B-cell ALL, Philadelphia chromosome positive ALL and Philadelphia chromosome positive CML. For the Applicants REINHOLD COHN AND PARTNERS By:
IL273432A 2017-09-22 2018-09-21 Protein degraders and uses thereof IL273432B (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201762562206P 2017-09-22 2017-09-22
US201762610403P 2017-12-26 2017-12-26
US201862714527P 2018-08-03 2018-08-03
PCT/US2018/052242 WO2019060742A1 (en) 2017-09-22 2018-09-21 Protein degraders and uses thereof

Publications (2)

Publication Number Publication Date
IL273432A IL273432A (en) 2020-05-31
IL273432B true IL273432B (en) 2022-09-01

Family

ID=65810510

Family Applications (3)

Application Number Title Priority Date Filing Date
IL273432A IL273432B (en) 2017-09-22 2018-09-21 Protein degraders and uses thereof
IL295603A IL295603B2 (en) 2017-09-22 2018-09-21 Protein degraders and uses thereof
IL307995A IL307995A (en) 2017-09-22 2018-09-21 Protein degraders and uses thereof

Family Applications After (2)

Application Number Title Priority Date Filing Date
IL295603A IL295603B2 (en) 2017-09-22 2018-09-21 Protein degraders and uses thereof
IL307995A IL307995A (en) 2017-09-22 2018-09-21 Protein degraders and uses thereof

Country Status (8)

Country Link
US (2) US11623932B2 (en)
EP (1) EP3684365A4 (en)
JP (2) JP7366031B2 (en)
AU (1) AU2018338314A1 (en)
CA (1) CA3076613A1 (en)
IL (3) IL273432B (en)
MX (2) MX2020003190A (en)
WO (1) WO2019060742A1 (en)

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7266526B6 (en) 2017-01-26 2024-02-15 アルビナス・オペレーションズ・インコーポレイテッド Estrogen receptor proteolytic modulators and related methods
WO2018237026A1 (en) 2017-06-20 2018-12-27 C4 Therapeutics, Inc. N/o-linked degrons and degronimers for protein degradation
WO2019060693A1 (en) 2017-09-22 2019-03-28 Kymera Therapeutics, Inc. Crbn ligands and uses thereof
EP3710002A4 (en) 2017-11-16 2021-07-07 C4 Therapeutics, Inc. Degraders and degrons for targeted protein degradation
EP3728207B1 (en) 2017-12-21 2023-02-01 Ribon Therapeutics Inc. Quinazolinones as parp14 inhibitors
WO2019133531A1 (en) 2017-12-26 2019-07-04 Kymera Therapeutics, Inc. Irak degraders and uses thereof
US11512080B2 (en) 2018-01-12 2022-11-29 Kymera Therapeutics, Inc. CRBN ligands and uses thereof
JP2021519337A (en) 2018-03-26 2021-08-10 シー４ セラピューティクス， インコーポレイテッド Cereblon binder for the degradation of Ikaras
CN112312904A (en) 2018-04-16 2021-02-02 C4医药公司 Spiro compounds
EP3817748A4 (en) 2018-07-06 2022-08-24 Kymera Therapeutics, Inc. Tricyclic crbn ligands and uses thereof
US20220348556A1 (en) 2018-07-06 2022-11-03 Kymera Therapeutics, Inc. Protein degraders and uses thereof
US11639354B2 (en) 2018-07-31 2023-05-02 Fimecs, Inc. Heterocyclic compound
AU2019353144B2 (en) 2018-10-05 2023-11-16 Annapurna Bio, Inc. Compounds and compositions for treating conditions associated with APJ receptor activity
AU2019389174A1 (en) 2018-11-30 2021-07-01 Kymera Therapeutics, Inc. Irak degraders and uses thereof
WO2020206424A1 (en) * 2019-04-05 2020-10-08 Kymera Therapeutics, Inc. Stat degraders and uses thereof
CN110058014B (en) * 2019-04-25 2021-06-04 中国科学院化学研究所 Products for screening LRPRC modulators and methods of identifying LRPRC modulators
JP7289510B2 (en) * 2019-05-08 2023-06-12 国立大学法人高知大学 Dementia drug screening method
CA3135592A1 (en) * 2019-05-20 2020-11-26 Xiaochao Ma Therapeutic agents for erythropoietic protoporphyria (epp) and x-linked protoporphyria (xlp)
JP2022540935A (en) 2019-07-17 2022-09-20 アルビナス・オペレーションズ・インコーポレイテッド TAU PROTEIN TARGETING COMPOUNDS AND RELATED METHODS OF USE
WO2021041942A1 (en) * 2019-08-28 2021-03-04 University Of Kentucky Research Foundation Collagen p4h1 inhibitor and its use
CN110596403B (en) * 2019-09-17 2022-12-16 中山大学附属第一医院 Specific protein marker for ovarian cancer diagnosis and preparation method thereof
CN110749733B (en) * 2019-12-06 2021-08-27 四川大学华西医院 Application of TGIF2LY autoantibody detection reagent in preparation of lung cancer screening kit
CA3161878A1 (en) 2019-12-17 2021-06-24 Matthew M. Weiss Irak degraders and uses thereof
US11591332B2 (en) 2019-12-17 2023-02-28 Kymera Therapeutics, Inc. IRAK degraders and uses thereof
EP4077319A1 (en) * 2019-12-20 2022-10-26 Calico Life Sciences LLC Protein tyrosine phosphatase degraders and methods of use thereof
JP2023509375A (en) 2019-12-20 2023-03-08 シーフォー セラピューティクス， インコーポレイテッド Isoindolinone and indazole compounds for the degradation of EGFR
AU2020412780A1 (en) 2019-12-23 2022-07-21 Kymera Therapeutics, Inc. SMARCA degraders and uses thereof
WO2021162493A1 (en) * 2020-02-14 2021-08-19 보로노이 주식회사 Protein kinase degradation inducing compound, and use thereof
CN111214664B (en) * 2020-02-24 2022-02-11 大连医科大学 Application of combination of USP2 and HSP90 inhibitor in inhibiting growth of ErbB2 positive breast cancer
MX2022010952A (en) 2020-03-05 2022-10-07 C4 Therapeutics Inc Compounds for targeted degradation of brd9.
EP3878847A1 (en) * 2020-03-13 2021-09-15 Centre Régional de Lutte contre le Cancer - Centre François Baclesse Bcl-2 family proteins modulating compounds for cancer treatment
EP4121055A4 (en) * 2020-03-17 2024-04-24 Kymera Therapeutics Inc Stat degraders and uses thereof
JP2023517393A (en) * 2020-03-17 2023-04-25 メッドシャイン ディスカバリー インコーポレイテッド Proteolytic modifier and method of use thereof
CA3171258A1 (en) 2020-03-19 2021-09-23 Nan JI Mdm2 degraders and uses thereof
WO2021236885A1 (en) * 2020-05-21 2021-11-25 Dana-Farber Cancer Institute, Inc. Piperidine-2,6-diones as small molecule degraders of helios and methods of use
TW202210483A (en) 2020-06-03 2022-03-16 美商凱麥拉醫療公司 Crystalline forms of irak degraders
KR102654220B1 (en) * 2020-07-07 2024-04-04 한국식품연구원 Pharmaceutical Composition for Preventing or Treating Fatty Liver Disease comprising CMIP inhibitor
TW202216686A (en) * 2020-07-16 2022-05-01 英屬開曼群島商百濟神州有限公司 Degradation of (egfr) by conjugation of egfr inhibitors with e3 ligase ligand and methods of use
CA3194492A1 (en) * 2020-10-07 2022-04-14 Kymera Therapeutics, Inc Stat degraders and uses thereof
EP4247381A1 (en) * 2020-11-20 2023-09-27 Foghorn Therapeutics Inc. Compounds and uses thereof
CN112899351B (en) * 2021-02-03 2022-08-26 东华大学 Double-fluorescence quantitative PCR detection kit for detecting cell infiltration state of PDX model mouse
WO2022216675A1 (en) * 2021-04-06 2022-10-13 Believe In A Cure, Inc. [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)- amino]-acetic acid for use in increasing foxg1 expression
JP2024515619A (en) 2021-04-16 2024-04-10 アルビナス・オペレーションズ・インコーポレイテッド Modulators of BCL6 Proteolysis and Related Methods of Use - Patent application
CN113186273B (en) * 2021-05-13 2023-02-21 中国人民解放军总医院第一医学中心 circRNA detection kit for predicting antiplatelet curative effect of P2Y12 receptor antagonist and application thereof
CA3223322A1 (en) * 2021-06-21 2022-12-29 Gesine Kerstin Veits Degrader compounds and uses thereof
WO2023283130A1 (en) 2021-07-04 2023-01-12 Newave Pharmaceutical Inc. Isoquinoline derivatives as mutant egfr modulators and uses thereof
CN113637750A (en) * 2021-07-16 2021-11-12 宁波市第一医院 Auxiliary diagnosis, prognosis diagnosis or risk stratification marker for acute myeloid leukemia and application thereof
CN113817818B (en) * 2021-10-22 2023-04-28 常州市第二人民医院 Tool for diagnosing allergic airway inflammation
CN113817833B (en) * 2021-10-26 2022-09-30 常州国药医学检验实验室有限公司 Kit for detecting cervical cell gene methylation based on fluorescent quantitative PCR technology and application
TW202339728A (en) * 2021-12-11 2023-10-16 美商凱麥拉醫療公司 Stat3 degraders and uses thereof
CN114656509B (en) * 2022-04-08 2024-05-24 国科温州研究院(温州生物材料与工程研究所) N-heterocyclic carbene-gold palladium alloy nanoparticle as well as preparation method and application thereof
WO2023225647A2 (en) * 2022-05-19 2023-11-23 University Of Puerto Rico Novel targets against ovarian cancer
WO2023250058A1 (en) * 2022-06-22 2023-12-28 Kymera Therapeutics, Inc. Stat degraders and uses thereof
WO2024006781A1 (en) 2022-06-27 2024-01-04 Relay Therapeutics, Inc. Estrogen receptor alpha degraders and use thereof
WO2024006776A1 (en) 2022-06-27 2024-01-04 Relay Therapeutics, Inc. Estrogen receptor alpha degraders and medical use thereof
CN115639306B (en) * 2022-12-26 2023-03-28 四川大学华西医院 Method for rapidly detecting concentration of antiepileptic drug in clinical sample
CN116813608B (en) * 2023-06-08 2024-03-22 英矽智能科技(上海)有限公司 Thiazole compound and application thereof

Family Cites Families (194)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4650750A (en) 1982-02-01 1987-03-17 Giese Roger W Method of chemical analysis employing molecular release tag compounds
US5650270A (en) 1982-02-01 1997-07-22 Northeastern University Molecular analytical release tags and their use in chemical analysis
US4709016A (en) 1982-02-01 1987-11-24 Northeastern University Molecular analytical release tags and their use in chemical analysis
US5516931A (en) 1982-02-01 1996-05-14 Northeastern University Release tag compounds producing ketone signal groups
US5360811A (en) 1990-03-13 1994-11-01 Hoechst-Roussel Pharmaceuticals Incorporated 1-alkyl-, 1-alkenyl-, and 1-alkynylaryl-2-amino-1,3-propanediols and related compounds as anti-inflammatory agents
JP3545461B2 (en) 1993-09-10 2004-07-21 エーザイ株式会社 Bicyclic heterocycle-containing sulfonamide derivatives
US6281230B1 (en) 1996-07-24 2001-08-28 Celgene Corporation Isoindolines, method of use, and pharmaceutical compositions
US6306663B1 (en) 1999-02-12 2001-10-23 Proteinex, Inc. Controlling protein levels in eucaryotic organisms
PT1382339E (en) 1999-12-10 2008-02-06 Pfizer Prod Inc Compositions containing pyrrolo ¬2,3-d pyrimidine derivatives
DE10002509A1 (en) 2000-01-21 2001-07-26 Gruenenthal Gmbh New substituted glutarimide derivatives are IL-12 antagonists, are useful as immunomodulators and for the treatment of angiopathy, hematological or oncological disorders
US6465507B2 (en) 2000-02-28 2002-10-15 Sugen, Inc. 3-(pyrolyllactone)-2-indolinone compounds as kinase inhibitors
PE20020354A1 (en) 2000-09-01 2002-06-12 Novartis Ag HYDROXAMATE COMPOUNDS AS HISTONE-DESACETILASE (HDA) INHIBITORS
US7041298B2 (en) 2000-09-08 2006-05-09 California Institute Of Technology Proteolysis targeting chimeric pharmaceutical
US7208157B2 (en) 2000-09-08 2007-04-24 California Institute Of Technology Proteolysis targeting chimeric pharmaceutical
EP1389617B1 (en) 2001-04-27 2007-01-03 Zenyaku Kogyo Kabushiki Kaisha Heterocyclic compound and antitumor agent containing the same as active ingredient
TWI329105B (en) 2002-02-01 2010-08-21 Rigel Pharmaceuticals Inc 2,4-pyrimidinediamine compounds and their uses
PT1536827E (en) 2002-08-14 2009-03-20 Silence Therapeutics Ag Use of protein kinase n beta
WO2004089925A1 (en) 2003-04-03 2004-10-21 Semafore Pharmaceuticals, Inc. Pi-3 kinase inhibitor prodrugs
BRPI0410870A (en) 2003-05-30 2006-07-04 Gemin X Biotechnologies Inc trieterocyclic compounds, compositions, and methods for treating cancer or viral diseases
JP2007524397A (en) 2003-07-03 2007-08-30 ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルベニア Inhibition of SYK kinase expression
JP4398263B2 (en) 2004-01-13 2010-01-13 富士通株式会社 Route design method
LT2612862T (en) 2004-05-13 2017-01-25 Icos Corporation Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
TWI380996B (en) 2004-09-17 2013-01-01 Hoffmann La Roche Anti-ox40l antibodies
BRPI0606318B8 (en) 2005-01-19 2021-05-25 Rigel Pharmaceuticals Inc compound, composition, and use of a compound
DK1866339T3 (en) 2005-03-25 2013-09-02 Gitr Inc GTR-binding molecules and their applications
EP2757099B1 (en) 2005-05-12 2017-08-23 AbbVie Bahamas Limited Apoptosis promoters
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
CN101248089A (en) 2005-07-01 2008-08-20 米德列斯公司 Human monoclonal antibodies to programmed death ligand 1(PD-L1)
US7402325B2 (en) 2005-07-28 2008-07-22 Phoenix Biotechnology, Inc. Supercritical carbon dioxide extract of pharmacologically active components from Nerium oleander
EP2364974A1 (en) 2005-10-07 2011-09-14 Exelixis, Inc. N-(3-Phenylamino-quinoxalin-2-yl)-benzenesulfonamide derivatives as phosphatidylinositol 3-kinase inhibitors
PL1951684T3 (en) 2005-11-01 2017-03-31 Targegen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases
RS54181B9 (en) 2005-12-13 2020-01-31 Incyte Holdings Corp Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as janus kinase inhibitors
AU2006332945C1 (en) 2005-12-23 2013-02-28 Wyeth Modified lysine-mimetic compounds
JO2660B1 (en) 2006-01-20 2012-06-17 نوفارتيس ايه جي PI-3 Kinase inhibitors and methods of their use
CA2650303C (en) 2006-04-26 2015-03-24 F. Hoffmann-La Roche Ag Thienopyrimidine pharmaceutical compounds and their use
EP2530083B1 (en) 2006-09-22 2016-04-27 Pharmacyclics LLC Inhibitors of bruton's tyrosine kinase
US20100279316A1 (en) 2007-01-19 2010-11-04 Leonid Gorelik Antibodies to Phosphorylated IRAK4
CA2702650C (en) 2007-03-12 2017-01-03 Ym Biosciences Australia Pty Ltd Phenyl amino pyrimidine compounds and uses thereof
WO2008118802A1 (en) 2007-03-23 2008-10-02 Regents Of The University Of Minnesota Therapeutic compounds
EP1987839A1 (en) 2007-04-30 2008-11-05 I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease
PE20090717A1 (en) 2007-05-18 2009-07-18 Smithkline Beecham Corp QUINOLINE DERIVATIVES AS PI3 KINASE INHIBITORS
PT2175884T (en) 2007-07-12 2016-09-21 Gitr Inc Combination therapies employing gitr binding molecules
EP2044949A1 (en) 2007-10-05 2009-04-08 Immutep Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response
JP2011514881A (en) 2007-11-09 2011-05-12 ザ ソルク インスティテュート フォー バイオロジカル スタディーズ Use of TAM receptor inhibitors as immunopotentiators and use of TAM activators as immunosuppressants
JP5583592B2 (en) 2007-11-30 2014-09-03 ニューリンク ジェネティクス コーポレイション IDO inhibitor
PT2288610T (en) 2008-03-11 2016-10-17 Incyte Holdings Corp Azetidine and cyclobutane derivatives as jak inhibitors
WO2009132238A2 (en) 2008-04-24 2009-10-29 Newlink Genetics Ido inhibitors
US8338439B2 (en) 2008-06-27 2012-12-25 Celgene Avilomics Research, Inc. 2,4-disubstituted pyrimidines useful as kinase inhibitors
AR072999A1 (en) 2008-08-11 2010-10-06 Medarex Inc HUMAN ANTIBODIES THAT JOIN GEN 3 OF LYMPHOCYTARY ACTIVATION (LAG-3) AND THE USES OF THESE
CN104479018B (en) 2008-12-09 2018-09-21 霍夫曼-拉罗奇有限公司 Anti- PD-L1 antibody and they be used to enhance the purposes of T cell function
US8921037B2 (en) 2008-12-16 2014-12-30 Bo Han PF4-depleted platelet rich plasma preparations and methods for hard and soft tissue repair
BR112012004823B1 (en) 2009-09-03 2021-11-30 Merck Sharp & Dohme Corp ANTIBODY OR ANTIGEN-BINDING FRAGMENT THEREOF, USE OF AN ANTIBODY OR ANTIGEN-BINDING FRAGMENT THEREOF, AND PHARMACEUTICAL COMPOSITION
JP2012254939A (en) 2009-10-07 2012-12-27 Astellas Pharma Inc Oxazole compound
ES2601226T3 (en) 2009-10-28 2017-02-14 Newlink Genetics Corporation Imidazole derivatives as IDO inhibitors
RU2565541C2 (en) 2009-12-10 2015-10-20 Ф.Хоффманн-Ля Рош Аг Antibodies primarily binding to extracellular domain 4 of human csf-1r, and using them
PH12018501083A1 (en) 2010-03-04 2019-02-18 Macrogenics Inc Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof
CA2789071C (en) 2010-03-05 2018-03-27 F. Hoffmann-La Roche Ag Antibodies against human csf-1r and uses thereof
US9169323B2 (en) 2010-03-05 2015-10-27 Hoffmann-La Roche Inc. Antibodies against human CSF-1R
US8114621B2 (en) 2010-03-12 2012-02-14 Saladax Biomedical Inc. Lenalidomide and thalidomide immunoassays
EP2566517B1 (en) 2010-05-04 2018-10-24 Five Prime Therapeutics, Inc. Antibodies that bind csf1r
EP2588129A4 (en) 2010-06-30 2014-07-09 Univ Brandeis Small-molecule-targeted protein degradation
CN105367577B (en) 2010-07-13 2019-04-23 弗·哈夫曼-拉罗切有限公司 Pyrazolo [1,5A] pyrimidine and thieno [3,2B] pyrimidine derivatives as IRAK4 regulator
PL2614082T3 (en) 2010-09-09 2019-02-28 Pfizer Inc. 4-1bb binding molecules
CN108864151A (en) 2010-11-19 2018-11-23 利亘制药公司 heterocyclic amine and application thereof
EP2649099A4 (en) 2010-12-07 2016-10-19 Univ Yale Small-molecule hydrophobic tagging of fusion proteins and induced degradation of same
MX347078B (en) 2010-12-09 2017-04-10 Univ Pennsylvania Use of chimeric antigen receptor-modified t cells to treat cancer.
PL2655357T3 (en) 2010-12-20 2016-12-30 Indazolyl triazole derivatives as irak inhibitors
US8703941B2 (en) 2011-01-10 2014-04-22 Nimbus Iris, Inc. IRAK inhibitors and uses thereof
US9169260B2 (en) 2011-03-22 2015-10-27 Merck Sharp & Dohme Corp. Amidopyrazole inhibitors of interleukin receptor-associated kinases
NO2694640T3 (en) 2011-04-15 2018-03-17
RU2625034C2 (en) 2011-04-20 2017-07-11 МЕДИММЬЮН, ЭлЭлСи Antibodies and other molecules binding b7-h1 and pd-1
WO2013042137A1 (en) 2011-09-19 2013-03-28 Aurigene Discovery Technologies Limited Bicyclic heterocycles as irak4 inhibitors
EP2773207B1 (en) 2011-10-31 2018-03-07 Merck Sharp & Dohme Corp. Aminopyrimidinones as interleukin receptor-associated kinase inhibitors
EA036814B9 (en) 2011-11-28 2021-12-27 Мерк Патент Гмбх Anti-pd-l1 antibody (embodiments), composition comprising this antibody and use thereof
RU2658603C2 (en) 2011-12-15 2018-06-21 Ф.Хоффманн-Ля Рош Аг Antibodies against human csf-1r and uses thereof
AU2013207972B2 (en) 2012-01-10 2017-06-15 Nimbus Iris, Inc. IRAK inhibitors and uses thereof
WO2013106646A2 (en) 2012-01-12 2013-07-18 Yale University Compounds and methods for the inhibition of vcb e3 ubiquitin ligase
RU2666530C2 (en) 2012-01-12 2018-09-11 Йейл Юниверсити Compounds and methods for enhanced degradation of target proteins and other polypeptides by an e3 ubiquitin ligase
ES2575604T3 (en) 2012-01-13 2016-06-29 Bristol-Myers Squibb Company Thiazolyl or thiadiazolyl substituted pyridyl compounds useful as kinase inhibitors
CN104159896B (en) 2012-01-13 2017-05-24 百时美施贵宝公司 Heterocyclic-substituted pyridyl compounds useful as kinase inhibitors
ES2630705T3 (en) 2012-01-13 2017-08-23 Bristol-Myers Squibb Company Triazolyl substituted pyridyl compounds useful as kinase inhibitors
EP2812355A4 (en) 2012-02-06 2016-03-02 Hoffmann La Roche Compositions and methods for using csf1r inhibitors
AR090263A1 (en) 2012-03-08 2014-10-29 Hoffmann La Roche COMBINED ANTIBODY THERAPY AGAINST HUMAN CSF-1R AND USES OF THE SAME
BR112014028013A2 (en) 2012-05-11 2018-02-27 Five Prime Therapeutics Inc methods for treating a condition associated with rheumatoid arthritis, rheumatoid arthritis, skin lesions, lupus nephritis, lupus, an inflammatory condition, cd16 + disorder, method for reducing the number of cd16 + monocytes, methods for slowing the progression of a renal condition, rag and bone loss
AR091649A1 (en) 2012-07-02 2015-02-18 Bristol Myers Squibb Co OPTIMIZATION OF ANTIBODIES THAT FIX THE LYMPHOCYTE ACTIVATION GEN 3 (LAG-3) AND ITS USES
MX2015000129A (en) 2012-07-10 2015-04-14 Ares Trading Sa Pyrimidine pyrazolyl derivatives.
IN2015DN00127A (en) 2012-07-11 2015-05-29 Nimbus Iris Inc
US20140018361A1 (en) 2012-07-11 2014-01-16 Nimbus Iris, Inc. Irak inhibitors and uses thereof
WO2014011902A1 (en) 2012-07-11 2014-01-16 Nimbus Iris, Inc. Irak inhibitors and uses thereof
KR20150047593A (en) 2012-08-31 2015-05-04 파이브 프라임 테라퓨틱스, 인크. Methods of treating conditions with antibodies that bind colony stimulating factor 1 receptor (csf1r)
KR20150058222A (en) 2012-09-19 2015-05-28 에프. 호프만-라 로슈 아게 2-oxo-2,3,4,5-tetrahydro-1h-benzo[b]diazepines and their use in the treatment of cancer
EP2903613B1 (en) 2012-10-08 2017-11-22 Merck Sharp & Dohme Corp. Pyrazole derivatives useful as inhibitors of irak4 activity
EP2903617B1 (en) 2012-10-08 2019-01-30 Merck Sharp & Dohme Corp. Inhibitors of irak4 activity
WO2014063061A1 (en) 2012-10-19 2014-04-24 Dana-Farber Cancer Institute, Inc. Hydrophobically tagged small molecules as inducers of protein degradation
WO2014074675A1 (en) 2012-11-08 2014-05-15 Bristol-Myers Squibb Company Heteroaryl substituted pyridyl compounds useful as kinase modulators
GB201311910D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel Compounds
WO2014121931A1 (en) 2013-02-07 2014-08-14 Merck Patent Gmbh Pyridazinone-amides derivatives
LT2953952T (en) 2013-02-07 2017-08-25 Merck Patent Gmbh Macrocyclic pyridazinone derivatives
EP2970334B1 (en) 2013-03-15 2018-05-23 Biogen MA Inc. Macrocyclic compounds as irak4 inhibitors for the treatment of inflammatory diseases
MX2016003843A (en) 2013-09-27 2017-02-15 Nimbus Iris Inc Irak inhibitors and uses thereof.
CA2929316C (en) 2013-11-08 2021-12-28 Takeda Pharmaceutical Company Limited Pyrazole for the treatment autoimmune disorders
BR112016008468A2 (en) 2013-11-18 2017-10-03 Hoffmann La Roche FORMULA COMPOUND, PHARMACEUTICAL COMPOSITION, COMPOUND, USE OF A COMPOUND, AND METHOD FOR THE TREATMENT OR IMPROVEMENT OF CANCER
AU2014354711B2 (en) 2013-11-27 2018-10-25 Signalchem Lifesciences Corporation Aminopyridine derivatives as TAM family kinase inhibitors
TWI667233B (en) 2013-12-19 2019-08-01 德商拜耳製藥公司 Novel indazolecarboxamides, processes for their preparation, pharmaceutical preparations comprising them and their use for producing medicaments
AR098991A1 (en) 2014-01-03 2016-06-22 Bristol Myers Squibb Co NICOTINAMIDE COMPOUNDS REPLACED WITH HETEROARILE
US10160753B2 (en) 2014-01-10 2018-12-25 Aurigene Discovery Technologies Limited Indazole compounds as IRAK4 inhibitors
IL284952B (en) 2014-01-13 2022-08-01 Aurigene Discovery Tech Ltd Bicyclic heterocyclyl derivatives as irak4 inhibitors
WO2015140133A1 (en) 2014-03-17 2015-09-24 F. Hoffmann-La Roche Ag Piperidine-dione derivatives
ES2910128T3 (en) 2014-04-04 2022-05-11 Pfizer Heteroaryl or bicyclo-fused aryl compounds and their use as IRAK4 inhibitors
US20160058872A1 (en) * 2014-04-14 2016-03-03 Arvinas, Inc. Imide-based modulators of proteolysis and associated methods of use
KR20240038809A (en) 2014-04-14 2024-03-25 아비나스 오퍼레이션스, 인코포레이티드 Imide-based modulators of proteolysis and associated methods of use
US20180228907A1 (en) 2014-04-14 2018-08-16 Arvinas, Inc. Cereblon ligands and bifunctional compounds comprising the same
RU2016140870A (en) 2014-04-22 2018-05-23 Нимбус Айрис, Инк. IRAK INHIBITORS AND THEIR APPLICATIONS
CU20160188A7 (en) 2014-06-20 2017-06-05 Aurigene Discovery Tech Ltd INDAZOLE COMPOUNDS SUBSTITUTED AS IRAK4 INHIBITORS
WO2015200795A1 (en) 2014-06-27 2015-12-30 Celgene Corporation Compositions and methods for inducing conformational changes in cereblon other e3 ubiquitin ligases
TW201613872A (en) 2014-07-18 2016-04-16 Biogen Ma Inc IRAK4 inhibiting agents
US20160022642A1 (en) 2014-07-25 2016-01-28 Yale University Compounds Useful for Promoting Protein Degradation and Methods Using Same
US10071164B2 (en) 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
WO2016053771A1 (en) 2014-09-30 2016-04-07 Merck Sharp & Dohme Corp. Inhibitors of irak4 activity
US9943516B2 (en) 2014-09-30 2018-04-17 Merck Sharp & Dohme Corp. Inhibitors of IRAK4 activity
US9932350B2 (en) 2014-09-30 2018-04-03 Merck Sharp & Dohme Corp. Inhibitors of IRAK4 activity
EP3200788B1 (en) 2014-09-30 2019-09-18 Merck Sharp & Dohme Corp. Inhibitors of irak4 activity
ES2772133T3 (en) 2014-11-20 2020-07-07 Merck Patent Gmbh Heteroaryl compounds as IRAK inhibitors and their uses
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2016105518A1 (en) 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
US20170327469A1 (en) 2015-01-20 2017-11-16 Arvinas, Inc. Compounds and methods for the targeted degradation of androgen receptor
EP3247708A4 (en) 2015-01-20 2018-09-12 Arvinas, Inc. Compounds and methods for the targeted degradation of the androgen receptor
EP3268367B8 (en) 2015-03-12 2022-11-16 Merck Sharp & Dohme LLC Carboxamide inhibitors of irak4 activity
WO2016144849A1 (en) 2015-03-12 2016-09-15 Merck Sharp & Dohme Corp. Thienopyrazine inhibitors of irak4 activity
EP3268004B1 (en) 2015-03-12 2019-12-18 Merck Sharp & Dohme Corp. Pyrrolopyridazine inhibitors of irak4 activity
EP3267996B1 (en) 2015-03-12 2020-11-11 Merck Sharp & Dohme Corp. Pyrazolopyrimidine inhibitors of irak4 activity
US10329295B2 (en) 2015-03-12 2019-06-25 Merck Sharp & Dohme Corp. Pyrrolotriazine inhibitors of IRAK4 activity
AU2016232705C1 (en) 2015-03-18 2021-06-17 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
GB201506871D0 (en) 2015-04-22 2015-06-03 Glaxosmithkline Ip Dev Ltd Novel compounds
BR112017022349B1 (en) 2015-04-22 2023-11-07 Rigel Pharmaceuticals, Inc COMPOUND, COMPOSITION UNDERSTANDING, ITS USES, AND, METHOD
EP3288558B1 (en) 2015-04-30 2022-05-11 Bayer Pharma Aktiengesellschaft Combinations of inhibitors of irak4 with inhibitors of btk
CN108136044B (en) 2015-06-04 2021-08-10 阿尔维纳斯运营股份有限公司 Imide-based proteolytic modulators and related methods of use
US20180147202A1 (en) 2015-06-05 2018-05-31 Arvinas, Inc. TANK-BINDING KINASE-1 PROTACs AND ASSOCIATED METHODS OF USE
ES2745525T3 (en) 2015-06-24 2020-03-02 Bristol Myers Squibb Co Heteroaryl-substituted aminopyridine compounds
CN105085620B (en) 2015-06-25 2018-05-08 中山大学附属第一医院 A kind of compound for targeting ubiquitination degraded Smad3
WO2017004134A1 (en) 2015-06-29 2017-01-05 Nimbus Iris, Inc. Irak inhibitors and uses thereof
WO2017004133A1 (en) 2015-06-29 2017-01-05 Nimbus Iris, Inc. Irak inhibitors and uses thereof
WO2017007612A1 (en) 2015-07-07 2017-01-12 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
CN108137507A (en) 2015-07-10 2018-06-08 阿尔维纳斯股份有限公司 Proteolysis conditioning agent and relevant application method based on MDM2
KR20180029061A (en) 2015-07-13 2018-03-19 아비나스 인코포레이티드 Alanine regulators of protein degradation and related uses
MX2018000512A (en) 2015-07-15 2018-04-13 Aurigene Discovery Tech Ltd Indazole and azaindazole compounds as irak-4 inhibitors.
MX2018000396A (en) 2015-07-15 2018-05-02 Aurigene Discovery Tech Ltd Substituted aza compounds as irak-4 inhibitors.
EP3337476A4 (en) 2015-08-19 2019-09-04 Arvinas, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
HUE053705T2 (en) 2015-08-27 2021-07-28 Pfizer Bicyclic-fused heteroaryl or aryl compounds as irak4 modulators
MX2018002986A (en) 2015-09-18 2018-05-02 Merck Patent Gmbh Heteroaryl compounds as irak inhibitors and uses thereof.
NZ739676A (en) 2015-09-18 2022-02-25 Merck Patent Gmbh Heteroaryl compounds as irak inhibitors and uses thereof
WO2017059280A1 (en) 2015-10-02 2017-04-06 The University Of North Carolina At Chapel Hill Novel pan-tam inhibitors and mer/axl dual inhibitors
WO2017079267A1 (en) 2015-11-02 2017-05-11 Yale University Proteolysis targeting chimera compounds and methods of preparing and using same
JP6895439B2 (en) 2015-12-22 2021-06-30 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Pyrazolo [1,5a] pyrimidine derivative as an IRAK4 regulator
WO2017117474A1 (en) 2015-12-30 2017-07-06 Dana-Farber Cancer Institute, Inc. Bifunctional compounds for her3 degradation and methods of use
WO2017117473A1 (en) 2015-12-30 2017-07-06 Dana-Farber Cancer Institute, Inc. Bifunctional molescules for her3 degradation and methods of use
US11427561B2 (en) 2016-01-20 2022-08-30 Biogen Ma Inc. IRAK4 inhibiting agents
CA3017740A1 (en) 2016-03-16 2017-09-21 Pearlie BURNETTE Small molecules against cereblon to enhance effector t cell function
US20170281784A1 (en) 2016-04-05 2017-10-05 Arvinas, Inc. Protein-protein interaction inducing technology
RU2021102253A (en) 2016-04-06 2021-03-03 Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган DESTRUCTORS OF MDM2 PROTEIN
JP7001614B2 (en) 2016-04-06 2022-02-03 ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン Monofunctional intermediate for ligand-gated target proteolysis
EP3455219A4 (en) 2016-05-10 2019-12-18 C4 Therapeutics, Inc. Amine-linked c3-glutarimide degronimers for target protein degradation
WO2017197036A1 (en) 2016-05-10 2017-11-16 C4 Therapeutics, Inc. Spirocyclic degronimers for target protein degradation
CN109641874A (en) 2016-05-10 2019-04-16 C4医药公司 C for target protein degradation3The glutarimide degron body of carbon connection
CN109562107A (en) 2016-05-10 2019-04-02 C4医药公司 Heterocycle degron body for target protein degradation
WO2017197056A1 (en) 2016-05-10 2017-11-16 C4 Therapeutics, Inc. Bromodomain targeting degronimers for target protein degradation
WO2017201069A1 (en) 2016-05-18 2017-11-23 Biotheryx, Inc. Oxoindoline derivatives as protein function modulators
PL3458101T3 (en) 2016-05-20 2021-05-31 F. Hoffmann-La Roche Ag Protac antibody conjugates and methods of use
WO2017205762A1 (en) 2016-05-27 2017-11-30 Pharmacyclics Llc Inhibitors of interleukin-1 receptor-associated kinase
WO2017205766A1 (en) 2016-05-27 2017-11-30 Pharmacyclics Llc Inhibitors of interleukin-1 receptor-associated kinase
WO2017207385A1 (en) 2016-05-31 2017-12-07 Bayer Pharma Aktiengesellschaft Substituted 3-methylindazoles, methods for the production thereof, pharmaceutical preparations containing same, and use thereof for the production of medicaments
GB201610147D0 (en) 2016-06-10 2016-07-27 Glaxosmithkline Ip Dev Ltd Novel compounds
WO2018005356A1 (en) 2016-06-27 2018-01-04 Rigel Pharmaceuticals, Inc. 2,4-diamino-pyrimidine compounds and method for making and using the compounds
US10646488B2 (en) 2016-07-13 2020-05-12 Araxes Pharma Llc Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof
JP2019196309A (en) 2016-09-15 2019-11-14 武田薬品工業株式会社 Heterocyclic compound
WO2018089736A1 (en) 2016-11-10 2018-05-17 Dana-Farber Cancer Institute, Inc. Degradation of protein kinases by conjugation of protein kinase inhibitors with e3 ligase ligand and methods of use
AU2017363313B2 (en) 2016-11-22 2021-06-24 Dana-Farber Cancer Institute, Inc. Inhibitors of interleukin-1 receptor-associated kinases and uses thereof
CN110612294B (en) 2017-01-31 2024-01-16 阿尔维纳斯运营股份有限公司 Human cerebulin ligands and bifunctional compounds comprising same
JOP20180011A1 (en) 2017-02-16 2019-01-30 Gilead Sciences Inc PYRROLO[1,2-b] PYRIDAZINE DERIVATIVES
PL3621960T3 (en) 2017-05-11 2021-11-08 Bristol-Myers Squibb Company Thienopyridines and benzothiophenes useful as irak4 inhibitors
WO2018237026A1 (en) 2017-06-20 2018-12-27 C4 Therapeutics, Inc. N/o-linked degrons and degronimers for protein degradation
EP3679026A1 (en) 2017-09-04 2020-07-15 C4 Therapeutics, Inc. Glutarimide
WO2019060693A1 (en) 2017-09-22 2019-03-28 Kymera Therapeutics, Inc. Crbn ligands and uses thereof
WO2019084030A1 (en) 2017-10-24 2019-05-02 Genentech, Inc. (4-hydroxypyrrolidin-2-yl)-hydroxamate compounds and methods of use thereof
EP3700901A1 (en) 2017-10-24 2020-09-02 Genentech, Inc. (4-hydroxypyrrolidin-2-yl)-heterocyclic compounds and methods of use thereof
EP3710002A4 (en) 2017-11-16 2021-07-07 C4 Therapeutics, Inc. Degraders and degrons for targeted protein degradation
US11065231B2 (en) 2017-11-17 2021-07-20 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides
WO2019133531A1 (en) 2017-12-26 2019-07-04 Kymera Therapeutics, Inc. Irak degraders and uses thereof
US11512080B2 (en) 2018-01-12 2022-11-29 Kymera Therapeutics, Inc. CRBN ligands and uses thereof
EP3737666A4 (en) 2018-01-12 2022-01-05 Kymera Therapeutics, Inc. Protein degraders and uses thereof
AU2019225166A1 (en) 2018-02-23 2020-08-06 Dana-Farber Cancer Institute, Inc. Small molecules for inducing selective protein degradation and uses thereof
WO2020010210A1 (en) 2018-07-06 2020-01-09 Kymera Therapeutics, Inc. Mertk degraders and uses thereof
US20220348556A1 (en) 2018-07-06 2022-11-03 Kymera Therapeutics, Inc. Protein degraders and uses thereof
EP3817748A4 (en) 2018-07-06 2022-08-24 Kymera Therapeutics, Inc. Tricyclic crbn ligands and uses thereof

Also Published As

Publication number Publication date
EP3684365A1 (en) 2020-07-29
AU2018338314A1 (en) 2020-04-09
JP2023175972A (en) 2023-12-12
IL295603B1 (en) 2023-11-01
JP2020534375A (en) 2020-11-26
IL295603B2 (en) 2024-03-01
MX2020003190A (en) 2020-11-11
US11623932B2 (en) 2023-04-11
CA3076613A1 (en) 2019-03-28
EP3684365A4 (en) 2021-09-08
WO2019060742A1 (en) 2019-03-28
MX2022013526A (en) 2022-11-16
US20230115184A1 (en) 2023-04-13
US20210238193A1 (en) 2021-08-05
IL273432A (en) 2020-05-31
IL307995A (en) 2023-12-01
IL295603A (en) 2022-10-01
JP7366031B2 (en) 2023-10-20

Similar Documents

Publication Publication Date Title
IL273432B (en) Protein degraders and uses thereof
AU2021200639B2 (en) PD-1/PD-L1 inhibitors
JP6703632B2 (en) Cytotoxic benzodiazepine derivative
JP2020534375A5 (en)
RU2683325C2 (en) New benzodiazepine derivatives
CN113683622A (en) Bioactive substance conjugate and preparation method and application thereof
IL278297B2 (en) Substituted heterocyclic inhibitors of ptpn11
CN110799218A (en) Antibody conjugates comprising STING agonists
TW201811793A (en) Pyrrolobenzodiazepines and conjugates thereof
CN112334194A (en) 3- (5-amino-1-oxoisoindolin-2-yl) piperidine-2, 6-dione derivatives and their use in the treatment of IKAROS family Zinc finger 2(IKZF2) dependent diseases
RU2014152115A (en) COMBINED THERAPY USING CLAUDIN ANTIBODIES 18.2 FOR TREATMENT OF CANCER
JP2010510215A5 (en)
TWI781145B (en) Maytansinoid derivatives with self-immolative peptide linkers and conjugates thereof
RU2014108043A (en) PHARMACEUTICAL COMPOSITION FOR TREATMENT AND / OR PREVENTION OF A MALIGNANT TUMOR
CN111757757A (en) Pyrrolobenzodiazepine antibody conjugates
RU2016129894A (en) COVALENTLY RELATED HELICAR-ANTIBODY CONJUGATES AGAINST HELICAR AND THEIR APPLICATION
RU2017139515A (en) PHARMACEUTICAL ACTIVE COMPOUNDS AS INHIBITORS OF RECEPTOR TYROSINKINASE OF THE FAMILY TAM
JP2022541749A (en) Peptide conjugates of cytotoxins as therapeutic agents
JP2010514686A5 (en)
AU2017214572A1 (en) Glucose conjugates of triptolide, analogs and uses thereof
JP7293108B2 (en) Combination therapy with Axl inhibitor and EGFR tyrosine kinase inhibitor
CN113260365A (en) Novel compound and pharmaceutical composition for enhancing anticancer activity comprising the same
RU2019111303A (en) ANTIBODIES AGAINST EDB AND ANTIBODY-DRUG CONJUGATES
AU2020311925A1 (en) Peptide conjugates of microtubule-targeting agents as therapeutics
CA3217997A1 (en) Anti-c-met antibody drug conjugates